EP1451145A1 - Novel crystalline polymorph of venlafaxine hydrochloride and methods for the preparation thereof - Google Patents
Novel crystalline polymorph of venlafaxine hydrochloride and methods for the preparation thereofInfo
- Publication number
- EP1451145A1 EP1451145A1 EP02782398A EP02782398A EP1451145A1 EP 1451145 A1 EP1451145 A1 EP 1451145A1 EP 02782398 A EP02782398 A EP 02782398A EP 02782398 A EP02782398 A EP 02782398A EP 1451145 A1 EP1451145 A1 EP 1451145A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- venlafaxine hydrochloride
- mammal
- venlafaxine
- hydrochloride
- crystalline polymorph
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/74—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/64—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Definitions
- This invention relates to a novel highly thermally stable anhydrous crystalline polymorphic form of venlafaxine hydrochloride, methods for the preparation thereof, and its use.
- Venlafaxine (1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol) and its therapeutically acceptable salts (collectively referred to as venlafaxine herein) are inhibitors of monoamine neurotransmitter uptake, a mechanism associated with clinical antidepressant activity. This mechanism has also been associated with reproductive function by affecting indirectly the hypothalamic-pituitary-ovarian axis. It is believed that venlafaxine's mechanism of action is related to potent inhibition of the uptake of the monoamine neurotransmitters serotonin and norepinephrine. To a lesser degree, venlafaxine also inhibits dopamine reuptake. However, it has no inhibitory activity on monoamine oxidase.
- venlafaxine In contrast to classical tricyclic antidepressant drugs, venlafaxine has virtually no affinity for muscaranic, histaminergic, or adrenergic receptors in vitro. Pharmacologic activity at these receptors is associated with the various anticholinergic, sedative, and cardiovascular effects seen with the tricyclic antidepressant drugs.
- Hypothalamic amenorrhea in depressed and non-depressed human females may also be treated with venlafaxine as taught in U.S. Patent No. 5,506,270.
- U.S. Patent No. 5,530,013 teaches that venlafaxine induces cognition enhancement and treats cognitive impairment in a mammal.
- U.S. Patent No. 5,744,474 discloses that venlafaxine can treat urinary incontinence in humans. More recently, as discussed in U.S. Patent No. 5,916,923, venlafaxine has been found to treat, prevent, and control obesity, generalized anxiety disorder, post- traumatic stress disorder, late luteal phase disphoric disorder (premenstrual syndrome), attention deficit disorder (with and without hyperactivity), Gilles de la Tourette syndrome, bulimia nervosa, and Shy Drager Syndrome in mammals (e.g., humans).
- the present invention provides a novel anhydrous crystalline polymorph of venlafaxine hydrochloride.
- the crystalline polymorph of the present invention exhibits characteristic XRPD peaks (expressed in degrees 2 ⁇ ) at about 5.67, 7.28, 9.14, 9.67, 10.77, 11.31 , 14.01,
- the crystalline polymorph of the present invention can be administered to a mammal to treat depression (including, but not limited to, major depressive disorder, bipolar disorder, and dysthymia), fibromyalgia, anxiety, panic disorder, agorophobia, post traumatic stress disorder, premenstrual dysphoric disorder (premenstrual snydrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder (including trichotillomania), social anxiety disorder, generalized anxiety disorder, autism, schizophrenia, obesity, anorexia nervosa, bulimia nervosa, Gilles de la Tourette Syndrome, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction (including premature ejaculation), borderline personality disorder, chronic fatigue syndrome, urinary incontinence, pain (including, but not limited to, migraine, chronic back pain, phantom limb pain, central pain, neuropathic pain such as diabetic neuropathy, and postherpetic neuropathy), Shy Drager Syndrome, or
- the crystalline polymorph can also be administered to prevent relapse or recurrence of depression, to induce cognitive enhancement, to treat cognitive impairment, and in regimens for cessation of smoking or other tobacco uses. Additionally, the crystalline polymorph can be administered to treat hypothalamic amenorrhea in depressed and non-depressed human females. These methods involve administering to a mammal (e.g., a human) in need thereof an effective amount of the crystalline polymorph of the present invention or a mixture of venlafaxine polymorphs that contains the crystalline polymorph of the present invention. Preferably, the venlafaxine is administered orally.
- compositions comprising the crystalline polymorph of the present invention and, optionally, a pharmaceutically acceptable carrier or diluent.
- the pharmaceutical composition comprises an amount of the crystalline polymorph effective to treat depression or any of the aforementioned indications in an animal, such as a mammal (e.g. human).
- the pharmaceutical composition comprises at least about 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99, 99.1 , 99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8, or 99.9% by weight of the crystalline polymorph of the present invention, based upon 100% total weight of venlafaxine hydrochloride in the pharmaceutical composition.
- the pharmaceutical composition comprises at least about 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99, 99.1 , 99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8, or 99.9% by weight of the crystalline polymorph of the present invention, based upon 100% total weight of venlafaxine hydrochloride in the pharmaceutical composition.
- the pharmaceutical composition may be incorporated into a dosage form, such as a tablet or capsule.
- the crystalline polymorph of the present invention can be prepared by heating venlafaxine hydrochloride of form I or II or mixtures thereof to a temperature of at least about 197°C and more preferably at least about 200°C. According to one embodiment, the venlafaxine hydrochloride is heated to about 200°C. Generally, the venlafaxine hydrochloride is heated for at least about 60 minutes and more preferably for at least about 150 minutes. The crystals formed may be recovered by any method known in the art.
- Another embodiment is a method of preparing a substantially pure crystalline polymorphic form of venlafaxine hydrochloride.
- the method includes obtaining the venlafaxine hydrochloride crystalline polymorph of the present invention in substantially pure form and then converting the substantially pure venlafaxine hydrochloride into another polymorphic form, such as form I.
- the substantially pure venlafaxine hydrochloride product can be incorporated into pharmaceutical compositions and dosage forms as known in the art.
- Figure 1 is a characteristic X-ray Powder Diffraction (XRPD) pattern of the anhydrous venlafaxine hydrochloride crystalline polymorph of the present invention.
- Figure 2 is a characteristic XRPD pattern of Form I of venlafaxine hydrochloride.
- Figure 3 is a characteristic XRPD pattern of Form II of venlafaxine hydrochloride.
- Figure 4 is a differential scanning calorimetry (DSC) scan of the anhydrous venlafaxine hydrochloride crystalline polymorph of the present invention carried out in a sealed pan at a scan rate of 10°C/minute from 25 to 240°C under a nitrogen purge.
- DSC differential scanning calorimetry
- FIG. 5 is a thermogravimetric analysis (TGA) of the anhydrous crystalline polymorph of the present invention heated from 28 to 238°C at a scan rate of 10°C/minute under a nitrogen purge.
- TGA thermogravimetric analysis
- the term “about” generally means within 10%, preferably within 5%, and more preferably within 1% of a given value or range. With regard to a given value or range in degrees 2 ⁇ from XRPD patterns, the term “about” generally means within 0.2° 2 ⁇ and preferably within 0.1°, 0.05°, or 0.01° 2 ⁇ of the given value or range. Alternatively, the term “about” means within an acceptable standard error of the mean, when considered by one of ordinary skill in the art.
- treat refers to preventing, ameliorating, controlling, or curing the desired symptoms or disorders.
- Venlafaxine hydrochloride refers to mixtures, e.g., racemic mixtures, of R and S-venlafaxine and their optically pure enantiomers.
- the crystalline polymorph of the present invention may be R, S, or a mixture, e.g., racemic mixture, of R and S-venlafaxine hydrochloride.
- the crystalline polymorph has an XRPD pattern substantially identical to that shown in Figure 1. Peak locations and intensities for the XRPD pattern in Figure 1 are provided in Table 1 below. Table 1
- the peaks (expressed in degrees 2 ⁇ ) at about 5.67, 7.28, 9.14, 9.67, 10.77, 14.01, 14.54, 16.17, 19.69, and 20.74 are unique to this crystalline polymorph.
- the crystalline polymorph also has a melting endotherm, according to differential scanning calorimetry, at 219°C.
- the crystalline polymorph of the present invention is useful for treating, preventing, or controlling depression and the aforementioned indications.
- the appropriate dosage amounts for an animal can be determined by methods known in the art. Generally, a therapeutic effective amount for the desired purpose is administered.
- the dosage of the crystalline polymorph of venlafaxine hydrochloride disclosed herein is generally from about 75 to about 300 mg per day.
- the crystalline polymorph can be formulated into a pharmaceutical composition.
- the pharmaceutical composition comprises an amount of the crystalline polymorph of venlafaxine hydrochloride effective to treat the desired indication in an animal, such as a human.
- the pharmaceutical composition comprises at least about 20, 30, 40, 50, 60, 70, 80,
- the pharmaceutical composition comprises at least about 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99, 99.1 , 99.2, 99.3, 99.4, 99.5,
- the pharmaceutical composition can also be substantially free or completely free of other crystalline polymorphs of venlafaxine hydrochloride, such as Forms I and II.
- the terms "substantially free” and “substantially pure” include those pharmaceutical compositions that contain less than 0.01 , 0.1 , 0.2, 0.3, 0.4, 0.5, 1 or 2% by weight of other crystalline polymorphs, such as Form I or II or both, based upon the total weight of pharmaceutical composition (or alternatively based upon on the total weight of venlafaxine hydrochloride in the pharmaceutical composition).
- the pharmaceutical composition contains from about 25 to about 350 mg of the crystalline polymorph of venlafaxine hydrochloride. More preferably, pharmaceutical compositions of the present invention contain 75 mg, 150 mg or 225 mg of the crystalline polymorph of venlafaxine hydrochloride.
- the pharmaceutical composition may also include one or more pharmaceutically acceptable carriers or diluents and excipients.
- excipient includes, but is not limited to, those materials that are acceptable for use in pharmaceutical formulations, and are added to the formulation to promote the stability and viability of the formulation, such as binders, bulking agents, clarifying agents, buffering agents, wetting agents, lubricants, sweeteners, and flavoring agents.
- Suitable excipients include, but are not limited to, cellulose, ethyl cellulose, gelatin, hydroxypropyl methylcellulose, iron oxide, titanium dioxide, lactose, magnesium stearate, and sodium starch glycolate.
- Suitable pharmaceutically acceptable carriers, diluents, and excipients also include those described in Remington's, The Science and Practice of Pharmacy, (Gennaro, A.R., ed., 19 th edition, 1995, Mack Pub. Co.) which is herein incorporated by reference.
- pharmaceutically acceptable refers to additives or compositions that are physiologically tolerable and do not typically produce an allergic or similar untoward reaction, such as gastric upset, dizziness and the like, when administered to an animal, such as a mammal (e.g. a human).
- the pharmaceutical composition is an extended release formulation, such as that described in U.S. Patent No. 6,274,171 , which is herein incorporated by reference.
- an extended release formulation may comprise spheroids comprised of the crystalline polymorph of the present invention, microcrystalline cellulose, and, optionally, hydroxypropyl- methylcellulose.
- the spheroids are preferably coated with a film coating composition comprised of ethyl cellulose and hydroxypropylmethylcellulose.
- the pharmaceutical composition may be a dosage form, such as a liquid (e.g., elixirs and suspensions), capsule, pill, or tablet.
- a liquid e.g., elixirs and suspensions
- the pharmaceutical compositions and the crystalline polymorph of venlafaxine hydrochloride may be administered to animals, including, but not limited to, mammals (e.g. humans), orally, intravenously, intramuscularly, parenterally intraperitoneally, subdermally, buccally, subcutaneously, transdermally, topically, rectally, vaginally, or intranasally.
- the composition is administered orally.
- the crystalline polymorph of the present invention can be prepared by heating venlafaxine hydrochloride of form I or II or mixtures thereof to at least about 197°C and more preferably at least about 200°C. According to one embodiment, the venlafaxine hydrochloride is heated to about 200°C. Generally, the venlafaxine hydrochloride is heated for a time sufficient to form the crystalline polymorph of the present invention. Preferably, the venlafaxine hydrochloride precursor is heated for at least about 60 minutes and more preferably for at least about 150 minutes.
- the crystalline polymorph may be prepared in substantially pure form by heating the venlafaxine hydrochloride precursor for a sufficient amount of time.
- Venlafaxine hydrochloride may be prepared by any method known in the art including, but not limited to, the methods described in U.S. Patent Nos. 4,535,186 and 4,761 ,501 and International Patent Publication Nos. WO 00/32555, WO 00/32556, and WO 01/07397, all of which are hereby incorporated by reference.
- the crystals formed may be recovered by any method known in the art, such as filtration, centrifugation, or with a Buchner style filter, Rosenmund filter, or plates and frame press. Typically, the crystals are recovered as solids.
- the crystalline polymorph can be converted into Form I by recrystallizing it in ethyl acetate in ethanol (e.g., 80% ethyl acetate in ethanol).
- substantially pure forms of the crystalline polymorph can be prepared such as by heating one or more forms of venlafaxine hydrochloride to about 200°C for a sufficient time.
- the substantially pure crystalline polymorph can be used to prepare other substantially pure crystalline polymorphic forms of venlafaxine hydrochloride, such as form I, by the methods described above.
- the substantially pure venlafaxine hydrochloride product can be incorporated into pharmaceutical compositions and dosage forms as known in the art.
- venlafaxine hydrochloride which is used as a raw material in the example below can be prepared by any method known in the art.
- venlafaxine hydrochloride of Form II was put in a glass vial, flushed with nitrogen gas and then sealed by heat.
- the sealed vial was put in an oil bath at about 200°C (197°C to 200°C) for 1 hour or until the shape of the crystals changed to form cream-white crystals.
- Example 1 The procedure in Example 1 was repeated with 500 mg of venlafaxine hydrochloride of Form II, except the vial was left in the oil bath for 2.5 hours instead of 1 hour.
- Example 1 The procedure in Example 1 was repeated, except an aluminum vial was used instead of a glass vial.
- XRPD was performed on the crystalline polymorph of venlafaxine hydrochloride of the present invention under dry conditions with a Scintag X2 X-Ray Diffraction System Model 00-A02, available from Thermo ARL of Ecublens, Switzerland.
- the XRPD instrument had the following parameters: Scan Type: Normal
- Type Fixed Slits X2 Configuration: No Tube: Type: Fixed Slits
- Example 5 Intrinsic Dissolution Rate
- the intrinsic dissolution rates of Form II and the crystalline polymorph of the present invention were determined as follows. Pellets of venlafaxine hydrochloride were prepared by compressing 100 mg of each material in a die (Wood's apparatus) at 1000 psi for 1 minute with a Carver press. The pellets produced were then fitted into a dissolution apparatus (Vankel 7010 equipped with a Cary 300 Ultraviolet/Visible Spectrophotometer) which resulted in a single exposed surface area of 0.5 cm 2 .
- the dissolution rate in 900 mL of water was determined by USP 23 (1995), section 711, page 1791 (Dissolution, apparatus 2), with a rotation speed of 100 rpm at 37°C.
- the dissolution media was circulated through a 1.0 cm path microflow cell at a flow rate of 10 mL/minute.
- Ultraviolet absorbance was recorded at 220 nm. Both Form II and the crystalline polymorph of the present invention exhibited dissolution rates of 24.7 mg/cm 2 -minute.
- DSC measurements on the anhydrous venlafaxine hydrochloride crystalline polymorph of the present invention were carried out in a sealed pan at a scan rate of 10°C/minute from 25°C to 240°C under a nitrogen purge with a Pyris I DSC available from Perkin-Elmer of Shelton, Connecticut.
- the DSC scan is shown in Figure 4.
- Figure 4 shows one endotherm at 221 °C (heat of fusion is 116 J/g), which was the melting of the anhydrous venlafaxine hydrochloride.
- the onset melting temperature for the venlafaxine hydrochloride was 219°C.
- a sample of the venlafaxine hydrochloride crystalline polymorph of the present invention was heated from 28 to 238°C at a scan rate of 10° C/minute in a Pyris I TGA, available from Perkin-Elmer of Shelton, Connecticut, under a nitrogen purge. The results are shown in Figure 5. The sample lost little weight until it was heated near the melting point of venlafaxine hydrochloride.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US33582201P | 2001-12-05 | 2001-12-05 | |
US335822P | 2001-12-05 | ||
PCT/US2002/038401 WO2003050075A1 (en) | 2001-12-05 | 2002-12-03 | Novel crystalline polymorph of venlafaxine hydrochloride and methods for the preparation thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1451145A1 true EP1451145A1 (en) | 2004-09-01 |
Family
ID=23313356
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP02782398A Withdrawn EP1451145A1 (en) | 2001-12-05 | 2002-12-03 | Novel crystalline polymorph of venlafaxine hydrochloride and methods for the preparation thereof |
Country Status (21)
Country | Link |
---|---|
US (2) | US7030164B2 (xx) |
EP (1) | EP1451145A1 (xx) |
JP (1) | JP2005511736A (xx) |
KR (1) | KR20050044673A (xx) |
CN (1) | CN1630631A (xx) |
AR (1) | AR037744A1 (xx) |
AU (1) | AU2002348266A1 (xx) |
BR (1) | BR0214742A (xx) |
CA (1) | CA2467593A1 (xx) |
CO (1) | CO5580818A2 (xx) |
EC (1) | ECSP045136A (xx) |
HU (1) | HUP0402524A2 (xx) |
IL (1) | IL162255A0 (xx) |
MX (1) | MXPA04005305A (xx) |
NO (1) | NO20042681L (xx) |
NZ (1) | NZ533363A (xx) |
PL (1) | PL370552A1 (xx) |
RU (1) | RU2004120285A (xx) |
TW (1) | TW200301101A (xx) |
WO (1) | WO2003050075A1 (xx) |
ZA (1) | ZA200405248B (xx) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020183553A1 (en) * | 2000-10-19 | 2002-12-05 | Ben-Zion Dolitzky | Crystalline venlafaxine base and novel polymorphs of venlafaxine hydrochloride, processes for preparing thereof |
CN100338028C (zh) * | 2000-10-31 | 2007-09-19 | 山道士有限公司 | 盐酸文拉法辛的晶形 |
RU2007102292A (ru) * | 2004-07-22 | 2008-08-27 | Вайет (Us) | Способ лечения расстройств и заболеваний нервной системы |
AU2005266997A1 (en) * | 2004-07-22 | 2006-02-02 | Wyeth | Method for treating nervous system disorders and conditions |
MX2007000848A (es) * | 2004-07-22 | 2007-03-26 | Wyeth Corp | Procedimiento para el tratamiento de trastornos y dolencias del sistema nervioso. |
WO2007013936A2 (en) * | 2005-07-21 | 2007-02-01 | Wyeth | Method for treating nervous system disorders and conditions |
JP2009511641A (ja) * | 2005-10-19 | 2009-03-19 | テバ ファーマシューティカル インダストリーズ リミティド | 高純度1−〔2−ジメチルアミノ−(4−メトキシフェニル)エチル〕シクロヘキサノール塩酸塩の調製方法 |
TWI446903B (zh) * | 2007-02-21 | 2014-08-01 | Sepracor Inc | 含(-)-o-去甲基泛拉弗辛(venlafaxine)之固體形式及其用途 |
CA2860747C (en) * | 2010-10-01 | 2015-08-11 | Shan Dong Luye Pharmaceutical Co., Ltd. | Polymorphs of 4-[2-dimethylamino-1-(1-hydroxycyclohexyl)ethyl]phenyl 4-methylbenzoate hydrochloride, methods for preparing the same and use of the same |
BR112015005894B1 (pt) | 2012-09-18 | 2022-03-29 | Auspex Pharmaceuticals, Inc | Composto, composição farmacêutica, método para tratar um distúrbio mediado por vmat2 e formulação farmacêutica de liberação prolongada |
KR102528845B1 (ko) | 2015-03-06 | 2023-05-08 | 오스펙스 파마슈티칼스, 인코포레이티드 | 비정상적 불수의 운동 장애의 치료 방법 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
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US4761501A (en) * | 1983-10-26 | 1988-08-02 | American Home Products Corporation | Substituted phenylacetamides |
US6440457B1 (en) | 1993-05-27 | 2002-08-27 | Alza Corporation | Method of administering antidepressant dosage form |
DE69429895T2 (de) * | 1993-06-28 | 2002-08-29 | American Home Products Corp., Madison | Neue Behandlungsmethoden durch Verwendung von Phenethylderivaten |
TW344661B (en) * | 1993-11-24 | 1998-11-11 | Lilly Co Eli | Pharmaceutical composition for treatment of incontinence |
US5530013A (en) * | 1994-02-14 | 1996-06-25 | American Home Products Corporation | Venlafaxine in the inducement of cognition enhancement |
US5506270A (en) * | 1995-01-30 | 1996-04-09 | American Home Products Corporation | Venlafaxine in the treatment of hypothalamic amenorrhea in non-depressed women |
US6274171B1 (en) * | 1996-03-25 | 2001-08-14 | American Home Products Corporation | Extended release formulation of venlafaxine hydrochloride |
UA77145C2 (en) * | 1997-11-05 | 2006-11-15 | Wyeth Corp | Extended release dosage formulation |
SK5762003A3 (en) | 2000-10-19 | 2003-11-04 | Teva Pharma | Crystalline venlafaxine base and novel polymorphs of venlafaxine hydrochloride, processes for preparing thereof |
US20020183553A1 (en) * | 2000-10-19 | 2002-12-05 | Ben-Zion Dolitzky | Crystalline venlafaxine base and novel polymorphs of venlafaxine hydrochloride, processes for preparing thereof |
CN100338028C (zh) * | 2000-10-31 | 2007-09-19 | 山道士有限公司 | 盐酸文拉法辛的晶形 |
WO2002046140A1 (en) | 2000-12-07 | 2002-06-13 | Dr. Reddy's Laboratories Ltd. | Novel crystalline polymorphic forms of venlafaxine hydrochloride and a process for their preparation |
UA77234C2 (en) * | 2001-12-05 | 2006-11-15 | Wyeth Corp | Monohydrate of venlafaxine hydrochloride and methods for its preparation (variants) |
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2002
- 2002-12-03 RU RU2004120285/04A patent/RU2004120285A/ru not_active Application Discontinuation
- 2002-12-03 BR BR0214742-4A patent/BR0214742A/pt not_active IP Right Cessation
- 2002-12-03 JP JP2003551102A patent/JP2005511736A/ja not_active Withdrawn
- 2002-12-03 MX MXPA04005305A patent/MXPA04005305A/es unknown
- 2002-12-03 WO PCT/US2002/038401 patent/WO2003050075A1/en active IP Right Grant
- 2002-12-03 CA CA002467593A patent/CA2467593A1/en not_active Abandoned
- 2002-12-03 TW TW091135027A patent/TW200301101A/zh unknown
- 2002-12-03 PL PL02370552A patent/PL370552A1/xx not_active Application Discontinuation
- 2002-12-03 IL IL16225502A patent/IL162255A0/xx unknown
- 2002-12-03 NZ NZ533363A patent/NZ533363A/en unknown
- 2002-12-03 AU AU2002348266A patent/AU2002348266A1/en not_active Abandoned
- 2002-12-03 CN CNA02824205XA patent/CN1630631A/zh active Pending
- 2002-12-03 HU HU0402524A patent/HUP0402524A2/hu unknown
- 2002-12-03 US US10/308,480 patent/US7030164B2/en not_active Expired - Fee Related
- 2002-12-03 EP EP02782398A patent/EP1451145A1/en not_active Withdrawn
- 2002-12-03 KR KR1020047008515A patent/KR20050044673A/ko not_active Application Discontinuation
- 2002-12-04 AR ARP020104689A patent/AR037744A1/es not_active Application Discontinuation
-
2004
- 2004-06-01 CO CO04050947A patent/CO5580818A2/es not_active Application Discontinuation
- 2004-06-04 EC EC2004005136A patent/ECSP045136A/es unknown
- 2004-06-25 NO NO20042681A patent/NO20042681L/no not_active Application Discontinuation
- 2004-07-01 ZA ZA200405248A patent/ZA200405248B/en unknown
-
2005
- 2005-11-21 US US11/284,157 patent/US20060074131A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
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See references of WO03050075A1 * |
Also Published As
Publication number | Publication date |
---|---|
NO20042681L (no) | 2004-06-25 |
NZ533363A (en) | 2005-10-28 |
WO2003050075A1 (en) | 2003-06-19 |
TW200301101A (en) | 2003-07-01 |
CN1630631A (zh) | 2005-06-22 |
BR0214742A (pt) | 2004-09-14 |
IL162255A0 (en) | 2005-11-20 |
CA2467593A1 (en) | 2003-06-19 |
US7030164B2 (en) | 2006-04-18 |
ZA200405248B (en) | 2005-10-03 |
HUP0402524A2 (hu) | 2005-03-29 |
US20060074131A1 (en) | 2006-04-06 |
RU2004120285A (ru) | 2005-04-10 |
US20030109585A1 (en) | 2003-06-12 |
AR037744A1 (es) | 2004-12-01 |
ECSP045136A (es) | 2004-07-23 |
CO5580818A2 (es) | 2005-11-30 |
AU2002348266A1 (en) | 2003-06-23 |
PL370552A1 (en) | 2005-05-30 |
MXPA04005305A (es) | 2004-09-13 |
JP2005511736A (ja) | 2005-04-28 |
KR20050044673A (ko) | 2005-05-12 |
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